Is RECQL4 p.Arg367Pro (c.1100G>C) pathogenic?

RECQL4 p.Arg367Pro (c.1100G>C) is classified Likely benign in RECQL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-19). AlphaMissense: likely benign (0.0907); Very rare (popmax 0.00439%, sas); Associated with Inborn genetic diseases.

What condition is associated with RECQL4 p.Arg367Pro (c.1100G>C)?

RECQL4 p.Arg367Pro (c.1100G>C) is associated with Inborn genetic diseases (ClinVar).

How common is RECQL4 p.Arg367Pro (c.1100G>C) in the general population?

RECQL4 p.Arg367Pro (c.1100G>C) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about RECQL4 p.Arg367Pro (c.1100G>C)?

AlphaMissense predicts likely benign (score 0.0907) — an in-silico prediction, not a clinical call.

RECQL4 p.Arg367Pro

c.1100G>C · VCV4863142

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0907 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0907	likely benign
SaProt	LLR -7.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.002	GERP -3.6
Regional constraint	o/e 1.39	unconstrained · MANE · 6,350 bp · p 1.8e-56 · regional, not allelic
Overall
CADD	3.08	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,030 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000373% 6/1,610,152 alleles · very rare exomes 6/1,457,838 · genomes 0/152,314 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,757
African / African-American	0.00133%	75,002
European (non-Finnish)	8.49e-05%	1,177,862

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: RECQL4
Protein: p.Arg367Pro
Coding: c.1100G>C
MANE Select: NM_004260
Type: single nucleotide variant
Location: chr8:144516019 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB

Full RECQL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RECQL4 p.Arg367Gln Uncertain significance ★★ ⚠ same residue
RECQL4 p.Arg367Gly Uncertain significance ★★ ⚠ same residue
RECQL4 p.Arg367Trp Uncertain significance ★★ ⚠ same residue
RECQL4 p.Arg367= Likely benign ★★ same residue
RECQL4 p.Arg367Leu Uncertain significance ★ ⚠ same residue
RECQL4 p.Ala1001Thr Uncertain significance ★★ ⚠ same condition
RECQL4 p.Ala1066Thr Uncertain significance ★★ ⚠ same condition
RECQL4 p.Ala1174Pro Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/recql4-p-arg367pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown